DESCRIPTION (Adapted from applicant's abstract and specific aims): The results from a large number of different experiments with SP-A and SP-D (lung collectins) in vitro suggest these two related proteins participate in at least two major physiologic processes: first, the regulation of lung surfactant homeostasis; and second, the non-specific innate immune response of the lung. The general objective of this project is to establish the physiological consequences of a deficiency in SP-A, SP-D or both proteins in mice to further our understanding of collectin function in the intact animal in health and disease. The specific aims are to: 1) generate mouse models of pulmonary collectin (SP-A and SP-D) deficiency by consecutive gene disruptions of the collectin locus; 2) characterize pulmonary mechanics and surfactant structure, function and extracellular metabolism in collectin deficient mice a) under normal, non-stressed conditions, b) during exercise, c) with protein-rich pulmonary edema and d) after reversing the phosphatidylglycerol to phosphatidylinositol (PG/PI) ratio in the surfactant phospholipids; and 3) determine if pulmonary collectin deficiency a) alters the susceptibility to spontaneous respiratory infection and b) increases the susceptibility to influenza A viral infection.